1. Field of the Invention
This invention is directed to novel high viscosity compositions and for methods for embolizing blood vessels. The compositions of this invention are particularly useful for treating aneurysms.
In one embodiment, the compositions of this invention comprise a biocompatible prepolymer and a biocompatible contrast agent. Upon delivery to a mammalian vascular site, the viscosity of these compositions is at least about 150 centistokes at 40° C. Polymerization of these compositions in vivo results in the formation of a solid, coherent mass which embolizes the vascular site.
In another embodiment, the compositions of the invention are heated to at least 40° C. and mixed to form a uniform suspension, transferred to a delivery catheter having a proximal end and a distal end, wherein the distal end is positioned in the vascular site to be embolized, and the composition is injected into the vascular site in sufficient amounts to embolize said site.
Publications
The following publications are cited in this application as superscript numbers:    1 Mandai et al., “Direct Thrombosis of Aneurysms with Cellulose Acetate Polymer”, 77 J. NEUROSURG. 497-500 (1992).    2 Kinugasa et al., “Direct Thrombosis of Aneurysms with Cellulose Acetate Polymer,” 77 J. NEUROSURG. 501-507 (1992).    3 Amdur et al., Cassarett and Doull's TOXICOLOGY, Editors, Pergamon Press, New York, 661-664 (1975).    4 Greff et al., U.S. Pat. No. 5,667,767, “Novel Compositions for Use in Embolizing Blood Vessels,” issued Sep. 16, 1997.    5 Greff et al., U.S. Pat. No. 5,580,568, “Cellulose Diacetate Compositions for Use in Embolizing Blood Vessels,” issued Dec. 3, 1996.    6 Kinugasa et al., “Early Treatment of Subarachnoid Hemmorrhage After Preventing Rerupture of an Aneurysm,” 83 J NEUROSURG. 34-41 (1995).    7 Kinugasa et al. “Prophylactic Thrombosis to Prevent New Bleeding and to Delay Aneurysm Surgery,” 36 NEUROSURG. 661 (1995).    8 Taki et al. “Selection and Combination of Various Endovascular Techniques in the Treatment of Giant Aneurysms,” 77 J. NEUROSURG. 37-42 (1992).    9 Castaneda-Zuniga, et al., “Interventional Radiology,” 1 VASCULAR EMBOLOTHERAPY Part 1, 9-32, Williams & Wilkins (1992).    10 Rabinowitz et al., U.S. Pat. No. 3,527,224, “Method of Surgically Bonding Tissues Together,” issued Sep. 8, 1970.    11 Hawkins et al., U.S. Pat. No. 3,591,676, “Surgical Adhesive Compositions,” issued Jul. 6, 1971.
All of the above publications are herein incorporated by reference in their entirety to the same extent as if each individual publication was specifically and individually indicated to be incorporated herein by reference in its entirety.
2. State of the Art
Embolization of blood vessels is conducted for a variety of purposes, including the treatment of tumors, lesions (such as aneurysms), uncontrolled bleeding, and the like.
Embolization as part of the treatment of aneurysms is preferably accomplished via catheter techniques which permit the selective placement of the catheter in the aneurysmal sac. In this regard, recent advancements in catheter technology, as well as in angiography, now permit neuroendovascular intervention including treatment of what would otherwise have been inoperable lesions.
Embolizing compositions, or embolic compositions, known in the art prior to Applicant's invention typically included a biocompatible polymer, a biocompatible solvent, and a contrast agent, which allowed for visualization of the in vivo delivery of the composition via fluoroscopy.1-8 The viscosity of the embolic compositions prior to Applicant's invention was typically low because only low-viscosity compositions could be delivered using conventional delivery technology.
Despite the many positive attributes of low-viscosity embolic compositions, certain problems did arise. For example, it was observed that low-viscosity embolic compositions migrated, solidified, and formed elongated, string-like masses distal from the point of ejection from the delivery catheter. This migration was observed to cause embolization not at the aneurysmal sac, but at arteries attendant to the aneurysmal sac. It was also observed that under high-flow conditions, the formed masses could fragment, which can lead to incapacitation or death of the patient.
This invention is based, in part, on the discovery that the formation of a solid, non-migratory mass having a substantially contiguous shape can be achieved by using embolic compositions comprising a biocompatible prepolymer and a biocompatible contrast agent wherein the composition has a viscosity of at least about 150 centistokes at 40° C.